Gianfagna Francesco, Poli Simone, Costanzo Simona, Di Castelnuovo Augusto, Panzera Teresa, De Curtis Amalia, Magnacca Sara, Persichillo Mariarosaria, De Santi Lorenzo, Cristofani Claudia, Loffredo Daniele, Cerletti Chiara, Donati Maria Benedetta, de Gaetano Giovanni, Iacoviello Licia
Research Center in Epidemiology and Preventive Medicine (EPIMED), Department of Medicine and Surgery, University of Insubria, Varese, Italy.
Novartis Farma SpA, Milan, Italy.
Front Cardiovasc Med. 2025 Jul 8;12:1571395. doi: 10.3389/fcvm.2025.1571395. eCollection 2025.
Epidemiological studies have revealed the role of lipoprotein(a) [Lp(a)] in the etiopathogenesis of cardiovascular disease (CVD). We analyzed the association between Lp(a) and the risk of a major cardiovascular event in subjects with previous CVD.
The analysis was conducted on the Moli-sani study population (24,325 individuals aged ≥35 years, recruitment from 2005 to 2010), focusing on subjects with prior CVD. Data from standardized questionnaires and blood pressure, anthropometric, and lab measurements were collected. Lp(a) levels were measured using biobanked samples. The cohort was followed for cardiovascular events. The association between Lp(a) levels and risk of major adverse cardiovascular events was analyzed using Kaplan-Meier and Cox regression models.
In total, 1,284 subjects reported a history of CVD at baseline. The mean ± SD Lp(a) level was 23.3 ± 26.0 mg/dl and 51 subjects (4.0%) had levels ≥90 mg/dl. After a median of 7.3 years, 307 CVD events were recorded and validated. Subjects belonging to the highest Lp(a) level group (≥90 mg/dl) showed a worse trend during early follow-up compared with the lowest level group (<30 mg/dl), with a peak during the first 18 months [hazard ratio (HR) = 3.43, 95% confidence interval (CI): 1.43-8.27]. This increase was higher in subjects with dyslipidemia not treated with statins and those with multiple previous CVD events (HR = 11.0, 95% CI: 1.98-61.1; HR = 25.6, 95% CI: 7.83-83.8).
High Lp(a) levels were associated with an increased risk of early secondary cardiovascular events in individuals with a history of multiple CVDs or non-treated dyslipidemia, suggesting that lipoprotein(a) is a modifiable biomarker that can be measured at different times for CVD risk assessment.
流行病学研究揭示了脂蛋白(a)[Lp(a)]在心血管疾病（CVD）发病机制中的作用。我们分析了Lp(a)与既往有CVD的受试者发生主要心血管事件风险之间的关联。
对莫利萨尼研究人群（24325名年龄≥35岁的个体，于2005年至2010年招募）进行分析，重点关注既往有CVD的受试者。收集来自标准化问卷的数据以及血压、人体测量和实验室检测数据。使用生物样本库中的样本测量Lp(a)水平。对该队列进行心血管事件随访。使用Kaplan-Meier和Cox回归模型分析Lp(a)水平与主要不良心血管事件风险之间的关联。
共有1284名受试者在基线时报告有CVD病史。Lp(a)水平的均值±标准差为23.3±26.0mg/dl，51名受试者（4.0%）的Lp(a)水平≥90mg/dl。在中位随访7.3年后，记录并验证了307例CVD事件。与最低水平组（<30mg/dl）相比，Lp(a)水平最高组（≥90mg/dl）的受试者在早期随访期间显示出更差的趋势，在最初18个月达到峰值[风险比（HR）=3.43，95%置信区间（CI）：1.43 - 8.27]。在未接受他汀类药物治疗的血脂异常患者和既往有多次CVD事件的患者中，这种增加更为明显（HR = 11.0，95%CI：1.98 - 61.1；HR = 25.6，95%CI：7.83 - 83.8）。
高Lp(a)水平与有多次CVD病史或未治疗的血脂异常个体早期继发性心血管事件风险增加相关，这表明脂蛋白(a)是一种可改变的生物标志物，可在不同时间进行测量以评估CVD风险。
